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Microfluidic Device for Recreating a Tumor Microenvironment in Vitro
Published on: November 20, 2011
An Integrated Microfluidics Approach for Personalized Cancer Drug Sensitivity and Resistance Assay
Inna Desyatnik1, Matan Krasner1, Ludmila Frolov1
1The Mina & Everard Goodman Faculty of Life Sciences and the Institute for Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, 52900, Israel.
Abstract:
Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell-based testing. Herein, presented is a microfluidic device that combines a drug microarray with cell microscopy. The device can perform 512 experiments to test chemosensitivity and resistance to a drug array. MCF7 and 293T cells are cultured inside the device and their chemosensitivity and resistance to docetaxel, applied at various concentrations, are determined. Cell mortality is determined as a function of drug concentration and exposure time. It is found that both cell types form cluster morphology within the device, not evident in conventional tissue culture under similar conditions. Cells inside the clusters are less sensitive to drugs than dispersed cells. These findings support a heterogenous response of cancer cells to drugs. Then demonstrated is the principle of drug microarrays by testing cell response to four different drugs at four different concentrations. This approach may enable the personalization of treatment to the particular tumor and patient and may eventually improve final patient outcome.
Insights
This study introduces a microfluidic device for personalized cancer medicine, revealing that clustered cancer cells show reduced drug sensitivity compared to dispersed cells, impacting treatment effectiveness.
Area of Science:
- Oncology
- Biomedical Engineering
- Drug Discovery
Background:
- Cancer is a leading global cause of death, necessitating effective and personalized treatments.
- Current cell-based drug testing is limited by difficulties in expanding patient tumor samples in culture.
- Personalized medicine seeks to tailor treatments to individual patients, but faces challenges in drug response prediction.
Purpose of the Study:
- To develop and validate a microfluidic device for high-throughput drug chemosensitivity testing.
- To investigate the differential drug response of cancer cells based on their morphology within the device.
- To demonstrate the potential of microfluidic drug microarrays for personalized cancer therapy.
Main Methods:
- A novel microfluidic device integrating a drug microarray and cell microscopy was designed.
- The device enabled 512 simultaneous experiments to test drug sensitivity and resistance.
- MCF7 and 293T cells were exposed to docetaxel at various concentrations, and cell mortality was assessed.
Main Results:
- Cancer cells formed distinct cluster morphologies within the microfluidic device, unlike conventional cultures.
- Cells within these clusters exhibited lower sensitivity to docetaxel compared to dispersed cells.
- The study confirmed heterogeneous drug responses within cancer cell populations.
Conclusions:
- Microfluidic devices can reveal complex cellular behaviors like cluster formation, influencing drug response.
- Drug microarrays on microfluidic platforms show promise for personalized cancer treatment strategies.
- This technology may lead to improved patient outcomes through tailored therapeutic interventions.
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